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An AMPK paradox in pulmonary arterial hypertension  [PDF]
Miranda Sun, Guofei Zhou
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.611136
Abstract:

Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric serine-threonine kinase important as a metabolic sensor for intracellular ATP levels and plays a key role in regulating cell survival and proliferation, particularly when cells are exposed to hypoxia. AMPK is critical for lung function, and abnormal AMPK signaling participates in many lung diseases. Recent studies suggest that both inhibition and activation of AMPK are preventive for the development of pulmonary arterial hypertension (PAH). However, the molecular mechanisms by which inhibition or activation of AMPK affects pulmonary hypertension (PH) appear to be distinct. Inhibition of AMPK by compound C blocks hypoxia-induced autophagy and induces apoptosis in pulmonary artery smooth muscle cells, leading to prevention of PAH; activation of AMPK by metformin attenuates the PH phenotype induced by hypoxia by regulating endothelial cell function. These seemingly opposing data on the function of AMPK in PH can be partly explained by off-target and compartment-specific effects of AMPK inhibitors and activators and the differentiated expression of AMPK in various cell types and subcellular locations. To elucidate the specific roles of AMPK in the pathogenesis of PAH, it is important to study the role of AMPK in a tissue specific manner combining genetic and biochemical approaches.

 

Boltzmann or Gibbs Entropy?
Thermostatistics of Two Models with Few Particles
 [PDF]

Enrique N. Miranda
Journal of Modern Physics (JMP) , 2015, DOI: 10.4236/jmp.2015.68109
Abstract: We study the statistical mechanics of small clusters (N ~ 10 - 100) for two-level systems and harmonic oscillators. Both Boltzmann’s and Gibbs’s definitions of entropy are used. The properties of the studied systems are evaluated numerically but exactly; this means that Stirling’s approximation was not used in the calculation and that the discrete nature of energy was taken into account. Results show that, for the two-level system, using Gibbs entropy prevents temperatures from assuming negative values; however, they reach very high values that are not plausible in physical terms. In the case of harmonic oscillators, there are no significant differences when using either definition of entropy. Both systems show that for N = 100 the exact results evaluated with statistical mechanics coincide with those found in the thermodynamic limit. This suggests that thermodynamics can be applied to systems as small as these.
Guidance Stabilization of Satellites Using the Geomagnetic Field
Francisco Miranda
International Journal of Aerospace Engineering , 2012, DOI: 10.1155/2012/231935
Abstract: In the last years the small satellites have played an important role in the technological development. The attractive short period of design and low cost of them and the capacity to solve problems that are usually considered as problems to big and expensive spacecrafts lead us to study the control problem of these satellites. Active three-axis magnetic attitude stabilization of a low Earth orbit satellite is considered in this work. The control is created by interaction between the magnetic moment generated by magnetorquers mounted on the satellite body and the geomagnetic field. This problem is quite complex and difficult to solve. To overcome this difficulty guidance control is considered, where we use ε-strategies introduced by Pontryagin in the frame of differential games theory. Qualitative analysis and results of numerical simulation are presented. 1. Introduction The problem of attitude control of spacecraft has been widely studied in the last years. If the spacecraft is equipped with three independent actuators, a complete solution to the set point and tracking control problems is available. This problem was solved by different ways (see, e.g., [1–4]). If only two independent actuators are available, as discussed in detail in [5], the problem of attitude regulation is not solvable by means of continuous time-invariant control laws, whereas a time-varying control law, achieving local asymptotic nonexponential stability, was proposed in [6]. Since magnetorquers are relatively reliable, lightweight, and energy efficient, they have become attractive for small and inexpensive satellites, but the above results are not directly applicable if the satellite is equipped with these magnetic coils as actuators. Such actuators operate on the basis of the interaction between the magnetic field generated by magnetic coils installed on the satellite body and the magnetic field of the Earth. This implies a spacecraft control significantly different. There are two classical uses of magnetic torque rods in attitude control. One is for momentum management of wheel-based systems [7]. The other is for angular momentum and nutation control of spinning [8], momentum-biased [9], and dual-spin spacecraft [10]. The present study is one of a growing number that considers active three-axis magnetic attitude stabilization of a low Earth orbit satellite considering a nontilted dipole model for the geomagnetic field. Magnetic coils have been extensively used since the early sixties as a simple and reliable technology to implement attitude control actuators in low Earth orbit
Pit-bull reviewing, the pursuit of perfection and the victims of success
Miranda Robertson
BMC Biology , 2011, DOI: 10.1186/1741-7007-9-84
Abstract: Meanwhile, our most viewed article for the past year has been Virginia Walbot's 'Are we training pit bulls to review our manuscripts?' [4].Ploegh, Petsko and Walbot have, with considerable eloquence and varying degrees of passion, described the problem that eLife is intended to address: the success of a postdoctoral Fellow in finding a good academic position is perceived to depend, and to a large extent probably does depend, on his or her having published a paper in one of the three highest-profile general biology journals; but getting a paper into one of those journals can be extraordinarily difficult because - it is widely felt (and see [1-3]) - referees seem to see it as their responsibility to insist on time-consuming additions and revisions, and editors are unable or unwilling to judge for themselves the justice of the referees' advice.Virginia Walbot [4] has suggested how the reviewer problem could be avoided by training graduate students to adopt a more constructive and judicious approach to refereeing. We have for the past three years or so been operating a policy of 're-review opt-out'[5]: authors who have been asked to make substantive revisions to their papers are also asked whether they wish the referees to see the revised version; if not, the decision is made by the editors (more below on how this policy has worked in practice).The solution proposed by eLife is to ensure quality, speed and justice by deploying a high-powered editorial board who will oversee the reviewing process and 150 highly selected biomedical experts who will do the reviewing; to avoid iterations by making a yes-or-no decision on first review; and to promote fairness and transparency by publishing the (anonymous) referees' reports. This is not very different in principle from the way that at least some other general biology journals operate; and the stated aims of eLife - to deliver quick, fair and intelligent ('high-quality') decisions - are, I imagine, shared by all journals aspir
Plus ?a change
Miranda Robertson
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-44
Abstract: That said, the fused publication will look and behave more like Journal of Biology than BMC Biology in most ways. We shall continue to publish the topical and authoritative review and comment that have regularly appeared in Journal of Biology, which will also bring its publication policy and speed of response to the fused journal (more on policy below). But listing on the Web of Science and Journal Citation Record will be as BMC Biology.In combining two journals, we are swimming against the tide of ever-proliferating new journals, a point remarked by Gregory Petsko in a Comment [2] written for us to mark the occasion and in which, with the verve and effrontery with which regular readers of his column in our sister journal Genome Biology will be familiar, he deplores such proliferation - inviting, perhaps, dissent. But we agree of course that this particular fusion is rational.In the combined journal, what is new, and what is not?To launch the new BMC Biology, we are publishing the first in an occasional series of special question-and-answer features, in which we invite biologists with a strong personal view on a subject of topical interest or fundamental importance to record a video interview which is posted online with the edited text, and so can be viewed or read, or both, according to preference. Our first interviewee is Martin Raff, the founding Editor-in-Chief of Journal of Biology and member of the Editorial Board of the fused journal. He speaks on autism [3], in which he developed a passionate interest when his grandson was diagnosed at a year and a half as autistic, and tackles issues ranging from the promise of genomic and induced stem cell technologies to the reasons for the apparent increase in incidence.The next Video Q&A, to be posted in May, will be from John Mattick, on the importance and roles of noncoding RNA - just as passionate, and - at least as concerns his perspective on biology - just as personal.We also have a new emblematic image (Figure 1).
The hope of progress
Miranda Robertson
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-39
Abstract: Two of the three contributions are reviews - by Christopher Lord and Alan Ashworth on the development of new cancer therapeutic drugs [2], and by Amy McKee, Megan McLeod, John Kappler and Philippa Marrack [3] on adjuvants and vaccine development. The third is a new feature, a video Q&A (see [4]), in which Martin Raff explains his interest in, and delivers his views on research on the biological basis of autism, both in video and in text format [5].Alan Ashworth and Christopher Lord are known for the ingenious application of poly(ADP-ribose) inhibitors to the treatment of BRCA-mutant tumors, an approach that migrated from laboratory bench to phase II clinical trials in less than five years. This work, an application of the synthetic lethal principle borrowed from genetic analysis and applied to tumor therapy, is described in their review, which traces the evolution of anti-cancer drugs from the cytotoxic blunt instruments that remain the principal weapons against cancer to date, through the more refined and sophisticated drugs - notably herceptin and imatinib - targeted at molecules known to be modified in specific tumors, and finally describes how an understanding of the workings of cells as a whole, and the entire panoply of changes that characterize a tumor cell, and not just a single mutant molecule, will become the basis of drug treatment.Vaccination, the first great empirical success of immunology, has, by comparison with the major chemotherapeutic drugs, the properties of a magic bullet. It is a remarkable fact, therefore, that despite an increasingly detailed appreciation of the workings of the immune system, the effectiveness of vaccines is still not properly understood. We understand that vaccination generates an adaptive immune response, usually protective antibodies; but this is the end result of a process of several cell-cell interactions that determine, first, whether there is an immune response at all; and second, whether that response is protective fo
The evolution of gene regulation, the RNA universe, and the vexed questions of artefact and noise
Miranda Robertson
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-97
Abstract: But the realization that the secret of evolution lies in changes in gene regulation considerably predates the revelations of genomics. Allan Wilson and colleagues, in a paper published in 1974 [1], drew attention to the simple and striking fact that morphologically homogeneous frog species also have relatively homogeneous karyotypes, whereas mammalian species, which are markedly diverse morphologically, also show major differences in chromosome number and organization; changes in proteins, by contrast, are much the same for both groups. They concluded that genome organization, and by implication gene regulation, is more important for metazoan evolution than protein sequence (and cite earlier publications of EB Ford and Susumu Ohno for the same insight). The following year, Mary-Claire King and Wilson published a more detailed examination of the chromosomal distinctions between human and chimpanzee [2], arguing compellingly, without benefit of high-throughput anything, that changes in the organization of the genome, and not changes in protein-coding sequence, must account for the crucial differences between the two primates.In those pre-genomic days, the protein data were in large part immunological and electrophoretic; the analysis of genome reorganization depended on chromosome banding patterns (Giemsa banding, not FISH); and almost nothing was known of the mechanism of gene regulation in eukaryotes. The ground between then and now is covered in a recent review by Sean Carroll [3], who acknowledges Emile Zuckerkandl and Eric Davidson as early proponents of the importance of gene regulation in morphological evolution and charts the remarkable history of the development of ideas consequent on the discovery of the homeobox genes, with a strong emphasis on the evolution of cis-regulatory elements - that is to say, DNA binding sites for gene regulatory proteins - as the basis for morphological change. The argument is that DNA regulatory elements and the proteins that bi
Expans?o da agricultura e sua vincula??o com o processo de urbaniza??o na Regi?o Nordeste/Brasil (1990-2010)
Miranda,Humberto;
EURE (Santiago) , 2012, DOI: 10.4067/S0250-71612012000200007
Abstract: the process of brazilian urbanization has changed in the last twenty years. studies in the regional economy have pointed to the strong influence of the expansion of export agriculture in areas of the border as a major determinant of the new urban dynamics in the period 1990-2008. statistics are used to describe the expansion of agriculture in the area of savannah in northeastern brazil, and to examine the possible effects it had on the process of urbanization in the period. the analysis of the effects of urbanization due to the expansion of agriculture is a consequence of growth for soybean exports to adjacent areas of the provinces of bahia (western bahia), maranh?o (south maranh?o) and piauí (southern piauí). we conclude that the pattern of urbanization in the northeast is characterized by a dynamic urban peripheral consequence of deepening social and spatial heterogeneity in recent years.
El presupuesto de culto en la Argentina y sus debates: Estado y sociedad ante el proceso de construcción de la Iglesia (1853-1880)
Lida,Miranda;
Andes , 2007,
Abstract: in order to understand what the creation of the catholic church state budget in 1853 meant it is not enough to take into consideration the presence of a liberal state which had the attribution to support the catholic worship. according to our point of view, it is also necessary to pay attention to the concept of state and church which justified and validated the existence of that budget in argentina. our premise is that its origin leads to a discussion not only about the relationship between state and church and the degree of autonomy of the latter as regards the first, but also about the relation between the process of formation of both, the argentine national state and the national catholic church. we must not forget that neither the church nor the state were fully consolidated in argentina when that budget was created. far from attempting against the church autonomy, it contributed to build the argentine church on a more solid basis than before. the tithe system, being very confused and contradictory, had been suppressed by the church reform in buenos aires in 1822, but it was still in use in the provinces of the country until 1853.
Comportamento intergrupal - revis?o de literatura
Miranda,Joana;
Análise Psicológica , 1998,
Abstract: in this article a literature review of an important area of social psychology, related to behaviour among groups, is presented. given the scope of this area, the present review only includes the following research topics: -individual processes in intergroup behaviour. -belonging to a group and intergroup behaviour. -intergroup behaviour and reduction of discrimination. the fact that the is based on this analysis are the concepts and theory of henri tajfel, it reflects my acknowledgment of the importance of this author in this field. however, i cannot but take a critical stand on some points of his theory, and to admit that a more complete review would involve the exploration of other lines of research, which in the meantime have been carried out by the geneve school.
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